Chemical space is basically infinite, and comprises all molecules that could possibly exist. Intelligent ways to efficiently navigate through chemical space and to select promising compounds in drug discovery are important tasks, and the focus of this thesis. In this work a new model for chemical space navigation, ChemGPS-NP, was developed. This model is based on a methodology where a global chemical space map is defined through principal component analysis of physico-chemical properties of a reference set of compounds. Through interpolation from the reference set, positions of novel compounds can be defined on this map and interpreted as chemical properties. ChemGPS-NP was demonstrated to be able to chart the entire biologically relevant chemical space, including both drug-like and natural compounds. This is an important improvement considering the present interest in natural products (NPs) in the pharmaceutical industry, as well as the track record of NPs to serve as basis for more than 50% of all marketed drugs. ChemGPS-NP proved able to handle and process large data sets, to aid in efficient selection of test objects, and to extract useful information from the results of high-throughput screening campaigns. Using ChemGPS-NP, it was shown that NPs occupy unique regions of chemical property space in comparison to drug-like compounds, and a number of features distinguishing NPs from medicinal chemistry compounds were identified. ChemGPS-NP was also shown to be able to reliably predict mode of action of anticancer agents based on chemical structure, a finding that has potential to improve cancer research efficiency. Applying a property based similarity search based on calculated eight dimensional Euclidean distances from ChemGPS-NP rendered a tool to identify NP inspired potential leads for drug discovery. Furthermore, ChemGPS-NPWeb, an online version of ChemGPS-NP, was developed, which provides scientists with open access to the tool via http://chemgps.bmc.uu.se/.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 5 uppsatser.

Não consta resumo na publicação. / Chamaecrista nictans subsp.patellaria var. ramosa Irwin & Barneby (Cassia Patellaria Dc), popularly know as \"peninha\", \"mata-pasto\", \"falsa-sensitiva\" e \"falsa-dormideira\", is Brazilian plant of the family Leguminosae. It is considered a garden and plantation weed, but in folk medicine is used for kidney problems and renal calculi. In order to identify their plant as a drug the morfology, histology, phytochemical screening, caracterization of fluid extract and plant powder were studied. In phytochemical screening the presence of flavonoid, saponins, steroids, tanins and coumarins was detected. A pharmacological assay was also carried out to test effect of chronic treatment with fluid extract in the experimental urolithiases in rats, through the development of calculi by surgical insertion of a foreign body their bladder. In rats, the results showed that chronic treatment with the same dosage of that used in folk medicine had no influence on the stones formed.

No description available.

Doutoramento em Farmacognosia / PhD Degree - Pharmacognosy

Red maple (Acer rubrum), also known as swamp, water or soft maple, is endemic to eastern and central North America and was widely used as traditional medicine by the first peoples. Commercially, its well-known products include maple syrup and high-quality lumber. The potential medicinal benefits of phenolic compounds extracted from the red maple plant, such as glucitol-core containing gallotannins, include antioxidant, and antiglycation effects as well as their importance in cosmetic applications. Plant-derived proteins and peptides are important biomolecules; however to date, there is no published data on the identification of proteins/peptides from red maple leaves. Therefore, the present study focuses on the activity guided purification of proteins from red maple leaves collected in spring and fall seasons. In addition, the focus of this project was in the evaluation of maple leaves employing bottom-up proteomics and De Novo protein profiling by PEAKS Studio-X and Gene Ontology Bioinformatics. The red maple leaves were grounded, defatted in hexane and proteins extracted in 25 mM sodium phosphate buffer pH 6.5. The extracted crude proteins were recovered by precipitation in 80% ammonium sulfate. The first-dimensional chromatography of crude extracted proteins was performed on a gel filtration column (HiLoad 16/600 Superdex200). The separation of crude extract and the partially purified gel filtration fraction was conducted by reversed-phase HPLC. The crude and eluted fractions were analyzed by SDS-PAGE gel electrophoresis. The extract was screened for cytotoxicity activity on Michigan Cancer Foundation-7 breast cancer (MCF-7), M.D. Anderson Metastasis Breast (MDA-MB-231) cancer cell lines and anti-inflammatory activity on murine macrophage (RAW 264.7) cell line from American Type Culture Collection (ATCC). The drug Doxorubicin was used as a positive control whereas untreated cells as a negative control in these experiments Preliminary data revealed that active protein fractions were eluted at two different regions of gel filtration chromatography both in spring and fall leaves. Bottom-up proteomics of crude and active fractions by PEAKS Studio-X and MASCOT bioinformatics database identified over 54 proteins. The Gene Ontology Annotation classified these proteins involved in the biological processing, cellular compartment, and molecular functions.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 6 uppsatser.

No description available.

No description available.

Doutoramento em Ciências Farmacêuticas / PhD in Pharmaceutical Sciences